Use of Antineoplastic Agents to Stimulate the Immune System for Treatment of Cancer

Abstract

Disclosed are methods useful for the therapeutic treatment of cancerous solid tumors by the administration of an antineoplastic agent, wherein the antineoplastic agent resides at the tumor site exposing the tumor to the antineoplastic agent for a sustained amount of time sufficient to stimulate the endogenous immune system of the subject resulting in the production of tumoricidal cells and infiltration of the tumoricidal cells in and around the tumor site at a level sufficient to treat the tumor. The methods include local administration methods such as topical application, pulmonary administration, intratumoral injection, and intraperitoneal injection.

1 . A method for treating a malignant solid tumor in a subject, the method comprising administering a composition comprising an antineoplastic agent to the subject, wherein the antineoplastic particles comprise taxane particles having a specific surface area (SSA) of at least 18 m 2 /g and a mean particle size (number) of from 0.1 microns to 5 microns, wherein the antineoplastic agent resides at the tumor site after administration of the composition exposing the tumor to the antineoplastic agent for a sustained amount of time sufficient to stimulate the endogenous immune system of the subject resulting in the production of tumoricidal cells and infiltration of the tumoricidal cells in and/or around the tumor site at a level sufficient to treat the tumor. 
     
     
         2 . The method of  claim 1 , wherein the sustained amount of time is at least 4 weeks. 
     
     
         3 . The method of  claim 1 , wherein the tumoricidal cells comprise dendritic cells, macrophages, T-cells, B cells, lymphocytes, or natural killer (NK) cells, or combinations thereof. 
     
     
         4 . The method of  claim 1 , wherein the administering comprises two or more separate administrations. 
     
     
         5 . The method of  claim 1 , wherein the administering comprises two or more separate administrations once a week for at least two weeks. 
     
     
         6 . The method of  claim 1 , wherein the administering comprises two or more separate administrations twice a week for at least one week, wherein the two or more separate administrations are separated by at least one day. 
     
     
         7 . The method of  claim 1 , wherein the treating comprises elimination of the tumor. 
     
     
         8 . The method of  claim 1 , wherein the administering is by local administration to the tumor. 
     
     
         9 . The method of  claim 8 , wherein the local administration is pulmonary administration, intratumoral injection administration, intraperitoneal injection administration, topical administration, intravesical instillation (bladder), or direct injection into tissues surrounding the tumor. 
     
     
         10 - 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the taxane particles comprise paclitaxel particles, docetaxel particles, cabazitaxel particles, or combinations thereof. 
     
     
         14 . The method of  claim 13 , wherein the taxane particles comprise at least 95% of the taxane. 
     
     
         15 . The method of  claim 13 , wherein the taxane particles are paclitaxel particles. 
     
     
         16 . The method of  claim 15 , wherein the paclitaxel particles have a specific surface area (SSA) of at least 18 m 2 /g. 
     
     
         17 . The method of  claim 13 , wherein the taxane particles are docetaxel particles. 
     
     
         18 . The method of  claim 17 , wherein the docetaxel particles have a specific surface area (SSA) of at least 18 m 2 /g. 
     
     
         19 . The method of  claim 1 , wherein, the taxane particles are not bound to, encapsulated in, or coated with one or more of a monomer, a polymer (or biocompatible polymer), a protein, a surfactant, or albumin. 
     
     
         20 . The method of  claim 1 , wherein the taxane particles are in crystalline form. 
     
     
         21 . The method  claim 1 , wherein the stimulation of the endogenous immune system produces a cellular immune response and/or a humoral immune response. 
     
     
         22 . The method of  claim 1 , wherein the treating comprises reducing metastases.